本文選題：椎間盤退行性疾病 + 髓核��； 參考：《生物化學與生物物理進展》2017年07期

【摘要】：椎間盤退變始發(fā)于髓核組織,獲得足夠有功能的髓核細胞是研究及治療椎間盤退變的關(guān)鍵.而人誘導多能干細胞(induced pluripotent stem cell,iPSC)不僅為建立疾病模型以研究疾病發(fā)生發(fā)展機制開辟了道路,還在再生醫(yī)學領(lǐng)域展現(xiàn)出了廣闊的應用前景.我們首先從椎間盤退變患者微創(chuàng)手術(shù)獲得的髓核組織內(nèi)分離髓核細胞,將攜帶OCT3/4、SOX2、KLF4和c-MYC的仙臺病毒(Sendai virus,Se V)轉(zhuǎn)染髓核細胞,重編程獲得iPSC.通過檢測多能細胞特異性標志、體內(nèi)成瘤實驗、甲基化及核型分析對所獲得的iPSC進行鑒定.并以皮膚成纖維細胞來源iPSC作為對照,在二維和三維水凝膠中對iPSC進行定向分化,檢測髓核細胞相關(guān)蛋白和基因的表達,比較分析2種iPSC向髓核細胞的分化效率.結(jié)果顯示,iPSC能表達多能細胞特異性標志,具有正常的二倍體核型,畸胎瘤實驗顯示三個胚層的出現(xiàn).誘導分化后的iPSC表達髓核相關(guān)基因和蛋白,在水凝膠中誘導培養(yǎng)后,iPSC表達更多的髓核相關(guān)基因和蛋白.髓核來源的iPSC與成纖維細胞來源的iPSC相比,可表達更多的髓核相關(guān)基因和蛋白.本研究首次將患者退變髓核細胞重編程成iPSC,并在水凝膠內(nèi)將其誘導分化為髓核樣細胞,為椎間盤退變個體化細胞治療奠定基礎(chǔ).
[Abstract]:Disc degeneration originated from nucleus pulposus tissue and the key to study and treat disc degeneration is to obtain enough functional nucleus pulposus cells.Human induced pluripotent stem cell induced pluripotent stem cell sci not only opens the way for the establishment of disease models to study the mechanism of disease occurrence and development, but also shows a broad application prospect in the field of regenerative medicine.We first isolated the nucleus pulposus cells from the nucleus pulposus tissue obtained from minimally invasive surgery in patients with disc degeneration. We transfected the nucleus pulposus cells with OCT3 / 4 SOX2KLF4 and Sendai virusSe V, and reprogrammed to obtain iPSCs.The iPSC was identified by detecting specific markers of pluripotent cells, tumorigenesis in vivo, methylation and karyotype analysis.IPSC derived from skin fibroblasts was used as control. IPSC was differentiated in two-dimensional and three-dimensional hydrogels to detect the expression of related proteins and genes in nucleus pulposus cells. The differentiation efficiency of two kinds of iPSC into nucleus pulposus cells was compared and analyzed.The results showed that iPSC could express pluripotent cell specific markers and had normal diploid karyotype. Teratoma test showed the appearance of three embryo layers.After induction and differentiation, iPSC expressed more genes and proteins of nucleus pulposus, and more genes and proteins of nucleus pulposus were expressed after induction and culture in hydrogel.Compared with iPSC derived from fibroblasts, iPSC derived from nucleus pulposus could express more genes and proteins associated with nucleus pulposus.In this study, the degenerative nucleus pulposus cells were reprogrammed into iPSCs for the first time, and induced to differentiate into nucleus pulposus like cells in hydrogel, which laid the foundation for individualized cell therapy of degenerative intervertebral disc.
【作者單位】： 深圳大學醫(yī)學部;深圳大學附屬第一醫(yī)院脊柱外科;
【基金】：國家自然科學基金(81301597) 深圳新興戰(zhàn)略產(chǎn)業(yè)發(fā)展專項資金(JCYJ20150525092940984/JCYJ20160422090807181)資助項目~~
【分類號】：R681.5

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